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Effectiveness, Safety and Immunogenicity of GSK Biologicals' HPV Vaccine GSK580299 (Cervarix TM) Administered in Healthy Adolescents

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00534638
First received: September 24, 2007
Last updated: May 5, 2016
Last verified: April 2016
  Purpose

Genital infections with oncogenic human papillomaviruses (HPV) are common in both men and women. The most important disease associated with oncogenic HPV infection is cervical cancer, currently the second leading cause of cancer-related death among women globally. The current study is designed to evaluate the overall impact of HPV immunization in adolescents 12-15 years of age.

This protocol posting has been updated following protocol amendment 09, 24 March 2014. The sections impacted are secondary objectives, endpoints, final analyses.


Condition Intervention Phase
Infections, Papillomavirus
Biological: GSK Biologicals' HPV Vaccine GSK580299
Biological: Engerix-B™
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Evaluation of the Effectiveness of Two Vaccination Strategies Using GlaxoSmithKline Biologicals' HPV Vaccine GSK580299 (Cervarix™) Administered in Healthy Adolescents

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Female Subjects With Vaccine Overall Effectiveness Against Genital Infection With Human Papilloma Virus (HPV) 16/18 Serotypes [ Time Frame: At the time of visit 5 (at 18.5 years of age) ] [ Designated as safety issue: No ]
    The analysis of overall effectiveness was based on stratified Mantel-Haenszel adjusted for clustering. The effectiveness was computed as 1- the prevalence odd ratio in all subjects from the investigated group (prevalence rate in all subjects from the investigated arm/prevalence rate in all subjects from Arm C).


Secondary Outcome Measures:
  • Number of Female Subjects With Vaccine Effectiveness Against Oropharyngeal Infection With HPV-16/18 Serotypes [ Time Frame: At the time of visit 5 (at 18.5 years of age) ] [ Designated as safety issue: No ]
    The analysis of total effectiveness was based on stratified Mantel-Haenszel adjusted for clustering. The effectiveness was computed as 1- the prevalence odd ratio in HPV vaccinated subjects from the investigated group (prevalence rate in HPV vaccinated subjects from the investigated arm/prevalence rate in all subjects from Arm C).

  • Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms, in a Subset of Subjects. [ Time Frame: Within 7 days (Days 0 - 6) after any vaccination ] [ Designated as safety issue: No ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. Relationship analysis was not performed.

  • Number of Subjects Reporting Any, Grade 3 and Related to Vaccination Solicited General Symptoms, in a Subset of Subjects. [ Time Frame: Within 7 days (Days 0 - 6) after any vaccination ] [ Designated as safety issue: No ]
    Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], gastrointestinal symptoms, headache, myalgia, rash and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

  • Number of Subjects Reporting Any, Grade 3 and Related to Vaccination Unsolicited Adverse Events (AEs), in a Subset of Subjects. [ Time Frame: Within 30 days (Days 0 - 29) after any vaccination ] [ Designated as safety issue: No ]
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

  • Number of Subjects Reporting Rash and Urticaria, in a Subset of Subjects. [ Time Frame: Within 30 minutes following vaccination ] [ Designated as safety issue: No ]
  • Number of Subjects Reporting Medically Significant Conditions (MSCs), in a Subset of Subjects. [ Time Frame: From Dose 1 (at Day 0) until Month 12 ] [ Designated as safety issue: No ]
    MSCs are defined as AEs prompting emergency room or physician visits that are not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that are not related to common diseases. Common diseases include: upper respiratory infections sinusitis, pharyngitis, gastroenteritis, urinary tract infections and injury.

  • Number of Subjects Reporting Any Serious Adverse Events (SAEs) and SAEs Causally Related to Vaccination, in a Subset of Subjects [ Time Frame: From Dose 1 (at Day 0) until Month 12 ] [ Designated as safety issue: No ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  • Number of Subjects Reporting SAEs Assessed by the Investigator as Possibly Related to Vaccination. [ Time Frame: During the entire study period up to the Visit 5 (18.5 years of age) ] [ Designated as safety issue: No ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  • Number of Subjects With HPV-16 and HPV-18 Antibody Concentrations Equal to or Above the Cut-off Values, by Gender, in a Subset of Subjects. [ Time Frame: At the time of Visit 1 (at Day 0), Visit 4 (at Month 7) and Visit 5 (at 18.5 years of age) ] [ Designated as safety issue: No ]
    The antibody concentrations against HPV-16 and HPV-18 were determined by Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 8 ELISA units per millilitre (EL.U/mL) for anti-HPV-16 and 7 EL.U/mL for anti-HPV-18 at Visits 1 and 4 and 19 EL.U/mL for HPV-16 and 18 EL.U/mL for HPV-18 at Visit 5. The Immunogenicity subset comprised the male study participants from the Cervarix/Engerix-B A Group plus female study participants from the same Cervarix/Engerix-B A Group.

  • Titres for Anti-HPV-16 and Anti-HPV-18 Antibodies, by Gender, in a Subset of Subjects. [ Time Frame: At the time of visits 1 and 4 (at Day 0 and Month 7) and at the time of Visit 5 (18.5 years of age) ] [ Designated as safety issue: No ]
    The antibody concentrations against HPV-16 and HPV-18 were determined by Enzyme-linked immunosorbent assay (ELISA). The cut-off of the assay was 8 ELISA units per millilitre (EL.U/mL) for anti-HPV-16 and 7 EL.U/mL for anti-HPV-18 at Visits 1 and 4 and 19 EL.U/mL for HPV-16 and 18 EL.U/mL for HPV-18 at Visit 5. The Immunogenicity subset comprised the male study participants from the Cervarix/Engerix-B A Group plus female study participants from the same Cervarix/Engerix-B A Group.

  • Number of Subjects Reporting Pregnancies With Onset During the Study [ Time Frame: Between Visit 1 (at Day 0) and Visit 5 (at 18.5 years of age) ] [ Designated as safety issue: No ]
    Pregnancies with onset during the study were classified by their outcome. Outcomes included live infant with no apparent congenital anomaly, elective termination with no apparent congenital anomaly, spontaneous abortion with no apparent congenital anomaly, ectopic pregnancy, stillbirth with no apparent congenital anomaly and molar pregnancy. One additional pregnant subject was lost to follow-up during the study.

  • Number of Female Subjects With New Onset of Autoimmune Diseases (NOADs). [ Time Frame: Between Visit 1 (at Day 0) and Visit 5 (at 18.5 years of age) ] [ Designated as safety issue: No ]
    NOADs include colitis ulcerative, juvenile arthritis, type 1 diabetes mellitus, coeliac disease and Chron's disease, Basedow's disease, erythema nodosum VIIth nerve paralysis and psoriasis.

  • Number of Female Subjects Reporting Any SAEs That Are Causally Related to Vaccination, in a Female Subjects [ Time Frame: During the entire study period (from Dose 1-Day 0 to Visit 5-18.5 years of age) ] [ Designated as safety issue: No ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  • Number of Male Subjects Reporting Any SAEs That Are Causally Related to Vaccination, in All Male Subjects [ Time Frame: During the entire study period (from dose1-Day 0 to Visit 5-18.5 years of age) ] [ Designated as safety issue: No ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.


Enrollment: 34206
Study Start Date: October 2007
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cervarix/Engerix-B A Group
90% of male and female adolescents will receive GSK Biologicals' HPV Vaccine GSK580299. Rest of the subjects will receive Engerix-B™ vaccine.
Biological: GSK Biologicals' HPV Vaccine GSK580299
Intramuscular injection, 3 doses
Biological: Engerix-B™
Intramuscular injection, 3 doses
Experimental: Cervarix/Engerix-B B Group
90% of the female adolescents will receive GSK Biologicals' HPV Vaccine GSK580299. Male adolescents and rest of the female adolescents will receive Engerix-B™ vaccine.
Biological: GSK Biologicals' HPV Vaccine GSK580299
Intramuscular injection, 3 doses
Biological: Engerix-B™
Intramuscular injection, 3 doses
Active Comparator: Engerix-B Group
All adolescents will receive Engerix-B™ vaccine.
Biological: Engerix-B™
Intramuscular injection, 3 doses

  Eligibility

Ages Eligible for Study:   12 Years to 15 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Study participants who the investigator or delegate believes that they and/or their parents/legally acceptable representative can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits) should be enrolled in the study.
  • A male or female between, and including, 12 and 15 years of age at the time of the first vaccination.

A written informed assent must be obtained from all study participants prior to enrolment. In addition, a written informed consent must be obtained from the study participants' parent or legally acceptable representative.

Note: As according to the Finnish law legal age of consent is 15 years, a written informed consent form can be obtained from study participants aged 15 years old and their parent(s)/legally acceptable representative(s) will receive a letter informing them of their child participation to the study.

  • Healthy male and female study participants as established by medical history before entering into the study. If needed, a history-directed clinical examination will be performed by the investigator or delegate (e.g. study nurse).
  • Study participants must not be pregnant. Absence of pregnancy should be verified (e.g. urine pregnancy test) as per investigator's or delegate's clinical judgement.
  • If the study participant is female, she must be of non-childbearing potential, i.e. be abstinent, have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal or pre-menarcheal, or if she is of childbearing potential, she must use adequate contraception for 30 days prior to vaccination and continue for 2 months after completion of the vaccination series.

Exclusion Criteria:

  • Previous vaccination against HPV or Hepatitis B virus.
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
  • Acute disease at the time of enrolment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhoea, mild upper respiratory infection with or without low-grade febrile illness, i.e. Oral temperature <37.5°C (99.5°F) / Axillary temperature <37.5°C (99.5°F) / Rectal temperature <38°C (100.4°F).)
  • Pregnant or lactating female.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00534638

Locations
Finland
GSK Investigational Site
Kotka, Finland, 48100
GSK Investigational Site
Kuopio, Finland, 70100
GSK Investigational Site
Lahti, Finland, 15110
GSK Investigational Site
Rauma, Finland, 26100
GSK Investigational Site
Tampere, Finland, 33100
GSK Investigational Site
Turku, Finland, 20100
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00534638     History of Changes
Other Study ID Numbers: 106636  2007-001731-55 
Study First Received: September 24, 2007
Results First Received: December 17, 2015
Last Updated: May 5, 2016
Health Authority: Finland: Finnish Medicines Agency

Keywords provided by GlaxoSmithKline:
HPV vaccine
Healthy adolescents
Cervical cancer
Safety
Immunogenicity
Cervarix

Additional relevant MeSH terms:
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016